Infants of diabetic mothers (I.D.M.) frequently develop prolonged and severe symptomatic neonatal hypoglycemia, an occurrence that may be associated with the development of permanent central nervous system dysfunction. While previous studies in I.D.M. have primarily examined alterations in hormonal environment, the role of insufficient hepatic glucose production in the genesis of neonatal hypoglycemia has not been systematically studied. We have recently characterized the perinatal development of the glucagon-sensitive adenylate cyclase system in the normal rat liver. This project is directed towards characterization of neonatal hepatic responsiveness to glucagon and insulin in infant rats of streptozotocin-induced diabetic mothers, and will include an analysis of 1) hepatic adenylate cyclase sensitivity to catabolic hormones, especially glucagon; 2) hormone (glucagon and insulin) binding to hepatic membranes from I.D.M.; 3) cyclic nucleotide (cAMP and cGMP) accumulation in isolated neonatal hepatocytes; 4) glycogenolysis and gluconeogenesis in isolated neonatal hepatocytes from I.D.M.; and 5) the effects of duration, severity and correction of maternal hyperglycemia, and maternal and neonatal glucose, insulin and glucagon concentrations on these hepatic biochemical processes. The results of the studies should provide new information on the mechanisms whereby maternal hyperglycemia may contribute to newborn hypoglycemia by limiting appropriate and necessary neonatal hepatic biochemical responses to this hypoglycemia.